Tumor Research Center of Integrative Medicine, Changhua Christian Hospital, Changhua, Changhua 50006, Taiwan, R.O.C.
Mol Med Rep. 2016 Feb;13(2):1263-8. doi: 10.3892/mmr.2015.4658. Epub 2015 Dec 8.
During progression of gastric cancer, degradation of the extracellular matrix by matrix metalloproteinases (MMPs) has been associated with poor prognosis. Tanshinone IIA (Tan-IIA) exerts antitumor activity in a variety of human cancer cells. It is extracted from Danshen (Salviae miltiorrhizae radix), and induces apoptosis and inhibits the proliferation of gastric cancer cells. However, the molecular mechanisms underlying the inhibition of migration in gastric cancer by Tan-IIA have not been fully elucidated. In the present study, AGS cell migration ability was evaluated using a wound-healing assay. The protein expression levels of nuclear factor (NF)-κB-p65, cyclooxygenase (COX)-2, MMP-2, -7, and -9 and β-actin in AGS cells were measured by western blotting. The results demonstrated that AGS cells treated with Tan-IIA exhibit decreased protein expression levels of NF-κB-p65, COX-2, and MMP-2, -7 and -9. The results also indicate that Tan-IIA inhibits migration ability in a dose- and time-dependent manner. These findings demonstrate that Tan-IIA inhibits the migration ability of AGS human gastric cancer cells and that decreasing the protein expression of NF-κB-p65, COX-2, and MMP-2, -7 and -9 may be an underlying molecular mechanism.
在胃癌的进展过程中,细胞外基质的降解与基质金属蛋白酶(MMPs)有关,与预后不良有关。丹参酮 IIA(Tan-IIA)在多种人类癌细胞中具有抗肿瘤活性。它从丹参(丹参根)中提取,可诱导细胞凋亡并抑制胃癌细胞的增殖。然而,Tan-IIA 抑制胃癌细胞迁移的分子机制尚未完全阐明。在本研究中,通过划痕愈合试验评估 AGS 细胞的迁移能力。通过 Western blot 测定 AGS 细胞中核因子(NF)-κB-p65、环氧化酶(COX)-2、MMP-2、-7 和 -9 以及β-肌动蛋白的蛋白表达水平。结果表明,Tan-IIA 处理的 AGS 细胞中 NF-κB-p65、COX-2 和 MMP-2、-7 和 -9 的蛋白表达水平降低。结果还表明,Tan-IIA 以剂量和时间依赖的方式抑制迁移能力。这些发现表明 Tan-IIA 抑制 AGS 人胃癌细胞的迁移能力,降低 NF-κB-p65、COX-2 和 MMP-2、-7 和 -9 的蛋白表达可能是其潜在的分子机制。